Passive immunization with rabbit antiserum to endotoxin prevented the Shwartzman reaction due to homologous and heterologous endotoxins. Homologous protection lasted at least 1 month, was conferred with the 19S fraction, and was accompanied by accelerated clearance of radioactive endotoxin from the circulating blood. Heterologous protection was not accompanied by accelerated clearance of endotoxin and bore no relationship to “0” antibody. Antiserum to the epimerase-deficient rough mutant J5 of Escherichia coli 0:111, which cannot incorporate “0” antigenic units, gave better protection than antiserum to smooth endotoxins. These results indicate that antiserum prevents the Shwartzman reaction by action against a toxic antigen common to endotoxins from unrelated bacterial genera; that loss of “0” antigenic units may enhance the production of protective antisera; and that accelerated clearance of endotoxin from the circulation is not necessary for protection.